Dose-Rate Dependence of Early Radiation Effects In Small Mammals

Abstract

In the course of laboratory experiments (1) directed toward evaluation of the biological effectiveness of monoenergetic fast neutrons in mice, it became necessary to consider quantitatively the effect of dose rate on the degree of response, particularly for the comparison irradiations with 250-kvp x-rays of 2 to 5 kev/µ linear energy transfer (LET). In addition to designing experiments for this evaluation, the literature was searched for data on dose-rate effects. The purpose of this paper is to compile and compare the results of the major dose-rate studies carried out in small mammals with ionizing radiations of low LET from external sources. It is with these studies that more data are available and the dose-rate effects more pronounced. Further, a formula will be derived that describes the relation of biological effectiveness to radiation dose rate in these studies. The significance of this expression will be discussed, and it will be compared briefly to formulas proposed by other investigators. A comprehensive analysis will not be undertaken of the numerous extensive treatments of radiotherapeutic data in man, from the earlier papers, such as those of Pack and Quimby (2) and Quimby and MacComb (3,4), to the more recent work of Friedman and Pearlman (5), Du Sault (6), and others, generally involving fractionated exposures. This paper will be limited to early effects on normal cells in animals generally treated with single (continuous) exposures, and the authors will not attempt to consider the necessarily more complex response of tumor cells, or the differential response of these and normal cells to variations of dose rate. For comparison purposes, however, certain data and theoretical curves for man will be cited. The degree of biological response to ionizing radiations of low LET has been long recognized as dependent on the length of time over which a given dose is administered. Numerous studies in recent years have revealed a marked dose-rate effect, based on a wide variety of criteria, in exposures to radiations of low LET. The few dose-rate studies made with radiations of higher LET (40 kev/µ and up), such as neutrons in the fission-energy range, revealed generally little or no dose-rate effect in acute or subacute exposures (7, 8). Few reviews have been made of the numerous published dose-rate studies in animals (with low LET radiations), and no single expression has been derived which may be applied to the bulk of results obtained. Less effort has been directed toward obtaining a relation which might pertain to data available in both small mammals and man. Compilation of Data The majority of the dose-rate studies in the literature employed thirty-day 50 per cent lethality (LD 50/30) as the criterion of effect. Although radiation death may result from failure of one or a combination of several cell systems, results with this criterion are reasonably reproducible.